Two Distinct Regulatory Systems Control Pulcherrimin Biosynthesis inBacillus subtilis

Abstract

Regulation of transcription is a fundamental process that allows bacteria to respond to external stimuli with appropriate timing and magnitude of response. In the soil bacteriumBacillus subtilis,transcriptional regulation is at the core of developmental processes needed for cell survival. Gene expression in cells transitioning from exponential phase to stationary phase is under the control of a group of transcription factors called transition state regulators (TSRs). TSRs influence numerous developmental processes including the decision between biofilm formation and motility, genetic competence, and sporulation, but the extent to which TSRs influence bacterial physiology remains to be fully elucidated. Here, we demonstrate two TSRs, ScoC and AbrB, along with the MerR-family transcription factor PchR negatively regulate production of the iron chelator pulcherrimin inB. subtilis.Genetic analysis of the relationship between the three transcription factors indicate that all are necessary to limit pulcherrimin production during exponential phase and influence the rate and total amount of pulcherrimin produced. Similarly, expression of the pulcherrimin biosynthesis geneyvmCwas found to be under control of ScoC, AbrB, and PchR and correlated with the amount of pulcherrimin produced by each background. Lastly, our in vitro data indicate a weak direct role for ScoC in controlling pulcherrimin production along with AbrB and PchR. The layered regulation by two distinct regulatory systems underscores the important, and somewhat enigmatic, role for pulcherrimin inB. subtilisphysiology.Author SummaryRegulation of gene expression is important for survival in ever changing environments. In the soil bacteriumBacillus subtilis,key developmental processes are controlled by overlapping networks of transcription factors, some of which are termed transition state regulators (TSRs). Despite decades of research, the scope of how TSRs influenceB. subtilisphysiology is still being uncovered. We found that three transcription factors, two of which are TSRs, converge to inhibit production of the iron-chelator pulcherrimin. Only when all three are missing is pulcherrimin production elevated. Finally, we demonstrate that expression of pulcherrimin biosynthesis genes occurs via direct and indirect regulation by the trio of transcription factors. Due to its iron chelating ability, pulcherrimin has been characterized as a modulator of niche development with antioxidant properties. Thus, our findings that TSRs control pulcherrimin, concurrently with other developmental phenotypes, provides new insight into how TSRs impactB. subtilisand its interaction with the environment.